Conversion Therapy of RAS/BRAF Wild-Type Right-sided Colon Cancer Patients With Initially Unresectable Liver Metastases

A Prospective Study on the Conversion Therapy of Ras / BRAF Wild Type Right-sided Colon Cancer Patients With Initially Unresectable Liver Metastases: Standard Chemotherapy Plus Cetuximab VS. Standard Chemotherapy Plus Bevacizumab

The prognosis of patients with metastatic right-sided colon cancer is worse than that of patients with metastatic left-sided cancer. Different guidelines have different recommendations on specific conversion therapy for colorectal liver metastases. The United States NCCN guidelines do not recommend standard chemotherapy combined with anti EGFR monoclonal antibody for patients with right colon cancer. The European ESMO guidelines recommend that patients with Ras / BRAF wild-type right-sided colon cancer should first consider three drugs ± bevacizumab, but considering the objective response rate results, standard chemotherapy + anti EGFR monoclonal antibody is still one of the choices. China CSCO guidelines recommend standard chemotherapy ± bevacizumab, and also recommend standard chemotherapy + cetuximab for patients with right-sided colon cancer.

Therefore, the targeted therapy for RAS / BRAF wild-type metastatic right colon cancer is still controversial. Therefore, we are ready to carry out the clinical trial of cetuximab and bevacizumab in conversion therapy for RAS / BRAF wild-type metastatic right colon cancer. The conversion resection rate is the primary point, and the objective response rate, perioperative safety and long-term survival are the secondary points.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Liver Metastases
• Intervention / Treatment: Drug: Cetuximab; Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy); Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Anticipated): 584
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The primary tumor was confirmed by histology as colorectal adenocarcinoma
2. primary right-sided colorectal adenocarcinoma
3. Radiologic evidence suggests that the initial unresectable liver metastases
4. RAS/BRAF gene wild-type states
5. ECOG was 0 ~ 1
6. Life expectancy ≥ 3 months
7. Good hematological function: neutrophil ≥ 1.5x109/l and platelet count ≥ 100x109 / L; HB ≥ 9g / dl (within one week before randomization)
8. Normal liver and kidney function: serum bilirubin ≤ 1.5x normal upper limit (ULN), alkaline phosphatase ≤ 5x ULN, serum transaminase (AST or ALT) ≤ 5x ULN (within one week before randomization);
9. Sign the written informed consent to participate in the experiment

Exclusion Criteria:

1. Patients with liver metastases from colorectal cancer who have previously received targeted therapy, chemotherapy, radiotherapy or interventional therapy
2. Known or suspected extrahepatic metastasis
3. Patients with known hypersensitivity to any component of the study treatment
4. Clinical related coronary heart disease or history of myocardial infarction in the last 12 months or left ventricular ejection fraction below normal range
5. Acute or subacute intestinal obstruction
6. Pregnancy (no pregnancy confirmed by serum / urine β - hCG) or breastfeeding.
7. She had other malignant tumors within 5 years, except for those with skin basal cell carcinoma or cervical cancer
8. Known drug / alcohol abuse
9. No legal capacity or limited legal capacity
10. There is peripheral neuropathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: standard chemotherapy plus Cetuximab	Drug: Cetuximab; mFOLFOX+Cetuximab for Ras / BRAF Wild Type Unresectable Right Colon Cancer Patients With Liver Metastasis; Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy); Standard Chemotherapy
Experimental: standard chemotherapy plus Bevacizumab	Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy); Standard Chemotherapy; Drug: Bevacizumab; mFOLFOX+Bevacizumab for Ras / BRAF Wild Type Unresectable Right Colon Cancer Patients With Liver Metastasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion liver resection rate	Rate of conversion from initially unresectable liver metastases to resectable ones	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	rate of objective response for therapy(according to RECIST 1.0)	up to 6 months
Incidence of adverse events	Incidence of adverse events	up to 6 months
Progression free survival	Progression free survival	up to 3 years
overall survival	overall survival	up to 5 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2020
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: August 23, 2020
• First Posted (Actual): August 25, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 23, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Bevacizumab; Colorectal Cancer; Cetuximab; Liver Metastases; right-sided
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Cetuximab
• Other Study ID Numbers: SHENKANG2020XU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No